The main objective was to formulate fast dissolving tablets of Amisulpride using a 32 full factorial design to study the effects of different concentrations of crospovidone and croscarmellose sodium on tablet properties. Nine formulations were prepared using combinations of 9%, 7%, or 5% crospovidone and 9%, 7%, or 5% croscarmellose sodium. Tablet properties like disintegration time, wetting time, and drug release at 50% and 90% were evaluated. Formulation F1 containing 9% of each superdisintegrant showed the fastest disintegration and drug release, most similar to the marketed product. Polynomial equations were derived relating the superdisintegrant concentrations to the response variables.

1. FABAD J. Pharm. Sci., 43, 2, 15-25, 2018
Formulation Development and Evaluation of
Amisulpride Fast Dissolving Tablets
Raghavendra KUMAR GUNDA*º
, Jujjuru Naga SURESH KUMAR*
RESEARCH ARTICLE
15
*
Department of Pharmaceutics, Narasaraopeta Institute of Pharmaceutical Sciences, Narasaraopet, Guntur (Dt), Andhra Pradesh, India-522601
° Corresponding Author; Mr.Raghavendra Kumar Gunda M.Pharm.,(Ph.D)
Assistant Professor, Department of Pharmaceutics,
Narasaraopeta Institute of Pharmaceutical Sciences,
Narasaraopet, Guntur(D.t), A.P. India-522601.
E-mail: raghav.gunda@gmail.com,
Mob: +91-9666705894.
Formulation Development and Evaluation of Amisulpride
Fast Dissolving Tablets
SUMMARY
The main objective of current research work was to formulate
Amisulpride fast dissolving tablets. Amisulpride, a second generation
antipsychotic agent, belongs to BCS class-II drug and used to treat
psychoses, paranoid, productive schizophrenias, dysthymia. Fast
dissolving tablets of amisulpride were prepared employing different
concentrations of crospovidone and croscarmellose sodium in different
combinations as a superdisintegrants by direct compression technique
using 32 factorial design. The concentration of crospovidone and
croscarmellose sodium was selected as independent variables, X1 and
X2 respectively whereas, wetting time, Disintegration time, t50%
,t90%were selected as dependent variables. nine formulations were
designed and are evaluated for hardness, friability, thickness, Assay,
Wetting time, Disintegration time, In-vitro drug release. From the
Results concluded that all the formulation were found to be with
in the Pharmacopoeial limits and the In-vitro dissolution profiles
of all formulations were fitted in to different Kinetic models,
the statistical parameters like intercept (a), slope (b) & regression
coefficient (r) were calculated. Polynomial equations were developed
for Wetting time, Disintegration time, t50%, t90%. Validity of
developed polynomial equations were verified by designing 2 check
point formulations (C1, C2). According to to SUPAC guidelines
the formulation (F1) containing combination of 9% crospovidone
and 9% croscarmellose, is the most similar formulation (similarity
factor f2=85.384, dissimilarity factor f1= 2.098& No significant
difference, t= 0.0585) to marketed product (SOLIAN-100). The
selected formulation (F1) follows First order, Higuchi’s kinetics,
mechanism of drug release was found to be Non-Fickian Diffusion
Super Case-II Transport (n= 1.445).
Key Words: Amisulpride, 32 factorial design, super disintegrants,
Wetting time, Disintegration time, Non-Fickian diffusion.
Received: 05.12.2017
Revised: 10.02.2018
Accepted: 15.02.2018
Hızlı Çözünen Amisülpirid Tabletlerin Değerlendirilmesi ve
Formülasyon Geliştirilmesi
ÖZET
Mevcut araştırma çalışmalarının temel amacı, Amisulpride hızlı
çözünen tabletleri formüle etmektir. Amisulpride ikinci nesil
antipsikotik bir ajandır, BCS sınıf II uyuşturucuya aittir ve psikozları,
paranoyak, üretken şizofreni, distimiyi tedavi etmek için kullanılır.
Amisülpirid’in hızlı çözünen tabletleri, 32 faktöriyel tasarım
kullanılarak doğrudan sıkıştırma tekniği ile farklı derişimlerde
süper dağıtıcı olarak farklı konsantrasyonlarda krospovidon ve
kroskarmeloz sodyum kullanılarak hazırlandı. Bağımlı değişken
olarak krospovidon ve kroskarmeloz sodyum konsantrasyonu sırasıyla
bağımsız değişken X1 ve X2 olarak seçilirken ıslanma süresi,
parçalanma zamanı, t5o%, t90% seçildi. Dokuz formülasyon
tasarlanmış ve sertlik, ufalanabilirlik, kalınlık, ıslatma süresi,
parçalanma süresi, in-vitro ilaç salınımı için değerlendirilmiştir.
Sonuçlardan, tüm formülasyonun farmakope sınırları içinde
olduğu ve tüm formülasyonların in-vitro çözünme profillerinin
farklı kinetik modellere uyduğu, kesişim noktası (a), eğim (b) ve
regresyon katsayısı (r) hesaplandı. Islatma süresi, parçalanma süresi,
t50%, t90% için polinomiyal denklemler geliştirildi. Geliştirilmiş
polinom denklemlerinin geçerliliği, 2 kontrol noktası formülasyonu
(C1, C2) tasarlayarak doğrulanmıştır. SUPAC kılavuzlarına göre,
% 9 krospovidon ve % 9 kroskarmellozun kombinasyonunu içeren
formülasyon (F1), pazarlanmış ürüne en benzer formülasyondur
(benzerlik faktörü f2 = 85.384, farksızlık faktörü f1 = 2.098 ve
önemli fark yok, t = 0.0585)(Amisülpirid-100). Seçilen formülasyon
(F1) takip edildi. Birinci mertebeden, Higuchi’nin kinetiği, ilaç
salınım mekanizması Non-Fickian Difüzyon Süper Durum II Nakil
(n = 1.445) olarak bulundu.
Anahtar Kelimeler: Amisülpirid, 32 faktöryel tasarım, süper
dağıtıcılar, Islanma zamanı, Dağılma zamanı, Non Fickian
difüzyon.

2. 16
Kumar Gunda, Suresh Kumar
INTRODUCTION
Fast dissolving tablets are suitable for numerous
kind of people , including for people who have swal-
lowing difficulties, pediatric, geriatric, and bedridden
patients. They are also useful for active patients who
are busy, travelling and may not have access to water.
Fast dissolving tablets are also popular as orodispers-
ible tablets, mouth-dissolving tablets, orally disinte-
grating tablets, melt-in mouth tablets, rapimelts, po-
rous tablets, quick dissolving etc (Kavitha et al., 2013).
Orally disintegrating tablets (ODT) are formulat-
ed by utilizing several processes, which differ in their
methodologies and the ODTs formed vary in various
properties such as, mechanical strength of tablet, taste
and mouth feel, swallowability, drug dissolution in
saliva, bioavailability and stability. Various processes
employed in formulating ODTs include freeze-dry-
ing or lyophilization, cotton candy process, molding,
spray drying, mass extrusion and compaction (wet
granulation, dry granulation, direct compression).
In the present study the direct compression meth-
od was adopted to manufacture the ODT tablets, since
it was very simple and do not require any sophisticat-
ed equipment’s. The direct compression represents the
simplest and most cost effective tablet manufacturing
technique (Thanda venkataramudu et al., 2012).
ODT by direct compression technique is a simple
approach of drug delivery systems that proved to be
rational in the pharmaceutical arena for its ease, com-
pliance, faster production, avoid hydrolytic or oxida-
tive reactions occurred during processing of dosage
forms.
Amisulpride is a benzamide analogue. The chem-
ical name of Amisulpride is 4-Amino-N-[[(2RS)-
1-thylpyrrolidin-2-yl]methyl]-5-(ethylsulpho-
nyl)-2-methoxybenzamide (Nirvesh Chaudari et al.,
2015; Hitesh P. Dalvadi et al., 2016). It blocks cerebral
dopamine D2
and D3
receptors. When administered
at an oral daily dose of 50 mg, it improves the dopa-
minergic neurotransmission with a D2
dopaminergic
receptors pre-synaptic inhibition and it is used in the
treatment of schizophrenia. Amisulpride ODT which
when placed in the tongue disintegrates or dissolves
rapidly in the saliva without the need of drinking wa-
ter. As tablet disintegrates in the mouth, this could en-
hance the clinical effect of the drug through pregastric
absorption from the mouth, pharynx and esophagus.
This leads to an increase in bioavailability by avoiding
first pass metabolism (M.A.Shende et al., 2014).
It is an important task to design an optimized
formulation with an appropriate dissolution rate in a
short time period with a minimum number of trials
or runs. Many statistical experimental designs have
been recognized as useful techniques to optimize the
process variables. For this purpose, response surface
methodology (RSM) utilizing a polynomial equation
has been widely used. Different types of RSM designs
include 3-level factorial design, central composite
design (CCD), Box-Behnken design and D-optimal
design. Response surface methodology (RSM) is used
when only a few significant factors are involved in
experimental optimization. The technique requires
less experimentation and time, thus proving to be far
more effective and cost-effective than the convention-
al methods of formulating rapid release dosage forms
(Schwartz BJ et al., 1996; Raghavendra Kumar Gunda
., 2015).
Hence an attempt is made in this research work to
formulate Fast Dissolving Tablets of Amisulpride us-
ing crospovidone and croscarmellose sodium. Instead
of normal heuristic method, a standard statistical tool
design of experiments is employed to study the effect
of formulation variables on the release properties.
Large scale production needs more simplicity in
the formulation with economic dosage form. The fast
dissolving tablets formulation by direct compression
method is most acceptable in industrial scale produc-
tion.
A 32
full factorial design was employed to system-
atically study the drug release profile . A 32
full fac-
torial design was employed to investigate the effect of
two independent variables (factors), i.e the amounts
of crospovidone and croscarmellose on the depen-
dent variables, i.e. Disintegration time, Wetting time,
t50%
, t90%
,( time taken to release 50%, 90% respective-
ly).
MATERIALS AND METHODS
Materials used in this study were obtained from
the different sources. Amisulpride was a gift sam-
ple from Dr.Reddy’s Laboratories, Hyderabad, India.
Avicel pH-101, crospovidone, croscarmellose, were
procured from Loba Chemie Pvt.Ltd, Mumbai. Other
excipients such as magnesium stearate, talc, vanillin
and sucralose were procured from S.D. Fine Chem.
Ltd., Mumbai.
Formulation development of amisulpride fast
dissolving tablets:
The factorial design is a technique that allows
identification of factors involved in a methodology
and assesses their relative priority. In addition, any
interaction between factors chosen can be identified.
Construction of a factorial design involves the selec-
tion of parameters and the choice of responses (Ramji
Anil Kumar Arza et al., 2016; NG RaghavendraRao et

3. 17
FABAD J. Pharm. Sci., 43, 2, 15-25, 2018
al., 2010).
A selected three level, two factor experimental
design (32
factorial design) describe the proportion
in which the independent variables Crospovidone
and Croscarmellose sodium are used in formulation
of Amisulpride fast dissolving tablets. The time re-
quired for 50% (t50%
), 90% (t90%
) drug dissolution, Dis-
integration Time and Wetting Time were selected as
dependent variables. Significance terms were chosen
at 95% confidence interval (p<0.05) for Final Equa-
tions. Polynomial equations were developed for t50%
,
t90%
, Disintegration time and Wetting time (step-wise
backward linear regression analysis).
The three levels of factor X1
(crospovidone) at a
concentration of 9%, 7%, 5%.Three levels of factor X2
(croscarmellose) at a concentration of 9%, 7%, 5%. (%
with respect to average weight of tablet, i.e 200 mg)
was taken as the rationale for the design of the Amisul-
pride fast dissolving tablet formulation. Amisulpride
fast dissolving tablet formulations were prepared em-
ploying selected combinations of the two factors i.e,
X1
, X2
as per 32
factorial design and evaluated to find
out the significance of combined effects of X1
, X2
to
select the best combination and the concentration re-
quired to achieve the desired fast release/ dissolution
of drug (by providing large surface area and improved
solubility) from the dosage form.
Preparation of Amisulpride Fast Dissolving Tab-
lets:
Amisulpride tablets were prepared by direct com-
pression method. The composition of each tablet is
shown in Table No 2. The drug, diluents, superdisite-
grants were passed through sieve #60 separately. All
the above ingredients were properly mixed together
(in a poly-bag). Talc and Magnesium stearate were
passed through mesh #80, mixed and blended with
initial mixture in a poly-bag. The powder blend was
compressed into tablets on a 8 station rotary punch
tableting machine (minipress) using 8 mm circular
punches and same hardness was used for the required
number tablets. Compressed tablets were examined as
per official standards and unofficial tests. Tablets were
packaged in well closed light resistance and moisture
proof containers.
Experimental Design:
Experimental design utilized in present investi-
gation for the optimization of superdisintegrant con-
centration such as, concentration of crospovidone
was taken as X1
and concentration of croscarmellose
sodium was taken as X2
. Experimental design was giv-
en in the Table 1. Three levels for the concentration
of crospovidone were selected and coded as -1= 5%,
0=7%, +1=9%. Three levels for the concentration of
croscarmellose sodium were selected and coded as
-1= 5%, 0=7%, +1=9%. Formulae for all the experi-
mental batches were given in Table 2 (Schwartz BJ et
al., 1996; Shiv Shankar Hardenia et al., 2014).
Table 1: Experimental design layout
Formulation Code X1
X2
F1
1 1
F2
1 0
F3
1 -1
F4
0 1
F5
0 0
F6
0 -1
F7
-1 1
F8
-1 0
F9
-1 -1
C1
-0.5 -0.5
C2
+0.5 +0.5
Table 2: Formulae for the preparation of Amisulpride fast dissolving tablets as per experimental design
Name of Ingredients
Quantity of ingredients per each tablet (mg)
F1
F2
F3
F4
F5
F6
F7
F8
F9
Amisulpride 100 100 100 100 100 100 100 100 100
Avicel pH-101 50 54 58 54 58 62 58 62 66
Crospovidone 18 18 18 14 14 14 10 10 10
Croscarmellose sodium 18 14 10 18 14 10 18 14 10
Magnesium Stearate 5 5 5 5 5 5 5 5 5
Talc 5 5 5 5 5 5 5 5 5
Sucralose 3 3 3 3 3 3 3 3 3
Vanillin 1 1 1 1 1 1 1 1 1
Total Weight 200 200 200 200 200 200 200 200 200

4. 18
Kumar Gunda, Suresh Kumar
Evaluation of amisulpride fast dissolving tablets:
Hardness
The hardness of the tablets was tested by diamet-
ric compression using a Monsanto hardness tester. A
tablet hardness of about 2-4 Kg/cm2
is considered ad-
equate for mechanical stability.
Friability
The friability of the tablets was measured in a
Roche friabilator (Camp-bell Electronics, Mumbai).
20 Tablets were taken, Weighed and Initial weight
was noted (W0
)arededusted in a drum for a fixed time
(100 revolutions, in a Roche friabilator) and weighed
(W) again. Percentage friability was calculated from
the loss in weight as given in equation as below. The
weight loss should not be more than 1 %.
Friability (%) = [(Initial weight- Final weight) /
(Initial weight)] x 100
Content Uniformity
In this test, 20 tablets were randomly selected and
the percent drug content was determined, the tab-
lets contained not less than 92.5% or not more than
107.5% (100±7.5%) of the labeled drug content can be
considered as the test was passed.
Assay
Drug content was determined by weighing ran-
domly selected tablets, pulverizing to a fine powder.
The powder equivalent to 100 mg Amisulpride was
weighed and dissolved in 10 ml of Distilled water in
volumetric flask, the volume was adjusted to 100 ml
with Phosphate buffer pH 6.8 and the solution was fil-
tered. An aliquot of 1.0 ml of solution were diluted to
10 ml Phosphate buffer pH 6.8 in separate volumetric
flask. The drug content was determined spectropho-
tometrically at 226 nm.
Thickness
Thickness of the all tablet formulations were mea-
sured using vernier calipers by placing tablet between
two arms of the vernier calipers.
Wetting time
To measure Wetting time of the tablet, a piece of
tissue paper folded twice was placed in a small petri
dish (internal diameter is= 6.5 cm) containing 5 ml of
distilled water. A Tablet placed on the paper, and the
time for complete wetting of the tablet was measured
in seconds.
In vitro dissolution study
The In vitro dissolution study for the Amisul-
pride fast dissolving tablets were carried out in USP
XXIII type-II dissolution test apparatus (Paddle type)
using 900 ml of Phosphate buffer pH 6.8 as dissolu-
tion medium at 50 rpm and temperature 37±0.5°C.
At predetermined time intervals, 5 ml of the samples
were withdrawn by means of a syringe fitted with a
pre-filter, the volume withdrawn at each interval was
replaced with same quantity of fresh dissolution me-
dium. The resultant samples were analyzed for the
presence of the drug release by measuring the absor-
bance at 226 nm using UV Visible spectrophotometer
after suitable dilutions. The determinations were per-
formed in triplicate (n=3).
Disintegration test
Disintegration of fast disintegrating tablets is
achieved in the mouth owing to the action of saliva,
however Quantity of saliva in the mouth is limited and
no tablet disintegration test was found in USP and IP
to simulate in vivo conditions. A modified method was
used to determine disintegration time of the tablets. A
cylindrical vessel was used in which 10 mesh screen
was placed in such way that only 2 ml of disintegrat-
ing or dissolution medium would be placed below
the sieve. To determine disintegration time, 6 ml of
Sorenson’s buffer (pH 6.8), was placed inside the ves-
sel in such way that 4 ml of the media was below the
sieve and 2 ml above the sieve. Tablet was placed on
the sieve and the whole assembly was then placed on a
shaker. The time at which all the particles pass through
the sieve was taken as a disintegration time of the tab-
let. 6 tablets were chosen randomly from the compos-
ite samples and the average value was determined.
Kinetic modelling of drug release
The dissolution profile of all the formulations was
fitted in to zero-order, first-order, Higuchi and Kors-
meyer-peppas models to ascertain the kinetic model-
ing of drug release (Notari RE., 1987;Higuchi., 1963;
Peppas., 1985).
RESULTS AND DISCUSSION
Fast dissolving tablets of Amisulpride were pre-
pared and optimized by 32
factorial design in order
to select the best composition of superdisintegrants,
crospovidone, croscarmellose sodium and also to
achieve the desired rapid release of drug from the dos-
age form (by disintegrating quickly). The two factorial
parameters involved in the development of formula-
tions are, quantity of crospovidone & croscarmellose
sodium as independent variables (X1
, X2
), and In vi-
tro dissolution parameters such as t50% ,
t90%
, Wetting
time and Disintegrating Time as dependent variables.
9 formulations were prepared using 3 levels of 2 fac-
tors and all the formulations containing 100 mg of
Amisulpride were prepared as a Fast dissolving tablet
dosage form by Direct Compression technique as per
the formulae given in Table 2.

5. 19
FABAD J. Pharm. Sci., 43, 2, 15-25, 2018
All the prepared tablets were evaluated for differ-
ent post compression parameters, drug content, mean
hardness, friability, mean thickness as per official
methods and results are given in Table 3. The hard-
ness of tablets was in the range of 3.31±0.57-3.81±0.28
Kg/cm2
. Weight loss in the friability test was not
more than 0.63%. Drug content of prepared tablets
was within acceptance range only. The wetting time
of tablets was in the range of 25.5±1.3-90.0±1.6 sec.
The disintegration time of tablets was in the range of
35.5±1.5-106.0±1.7 sec. Results for all Post-compres-
sion parameters were tabulated or shown in Table 3.
In-vitro dissolution studies were performed for
preparedtabletsusingPhosphatebufferpH6.8asadis-
solution media at 50 rpm and temperature 37±0.5°C.
The In-vitro dissolution profiles of tablets are shown in
Fig.1-4 (kinetic plots), wetting time chart, disintegra-
tion time charts were shown in Fig.5-6.
The dissolution parameters are given in Table 4.
Cumulative % drug release of factorial design formu-
lations F1
-F9
at 25 mins were found to be in the range
of 89.06-99.33 %. From the result it reveals that the
release rate was higher for formulations containing
high level of crospovidone/croscarmellose sodium
compared with other formulations containing lower
level, due to high concentration of superdisintegrant
in combination, shows various disintegration mecha-
nism such as wicking and swelling etc more compared
with lower concentration and alone, drug may release
rapidly and shows improved bioavailability. Excess of
superdisintegrant also prone to friable. therefore, re-
quired release of drug can be obtained by manipulat-
ing the composition of crospovidone and croscarmel-
lose sodium.
variation was observed in the Wetting time, Dis-
integrating time, t50%
and t90%
due to formulation vari-
ables. formulation F1
containing 18 mg of crospo-
vidone, 18 mg of croscarmellose sodium showed
promising dissolution parameter (Wetting time=
25.5±1.3sec, Disintegrating time =
35.5±1.5 sec , t50%
=
2.679 min , t90% =
8.902 min). The difference in burst
effect of the initial time is a result of the difference
in the concentration of superdisintegrants mixtures.
This reveals that increased concentration of super-
disintegrants resulted in a corresponding decrease in
the Wetting time, which might be due to the result
of wicking and other possible disintegrating mecha-
nisms. Disintegration time is directly proportional to
wetting time.
The In vitro dissolution data of Amisulpride fast
dissolving formulations was subjected to goodness of
fit test by linear regression analysis according to zero
order and first order kinetic equations, Higuchi’s and
Korsmeyer-Peppas models to assess the mechanism
of drug release. The results of linear regression anal-
ysis including regression coefficients are summarized
in Table 4. It was observed from the above that disso-
lution of all the tablets followed First order kinetics
with co-efficient of determination (R2
) values in the
range of 0.974-0.999. The values of r of factorial for-
mulations for Higuchi’s equation was found to be in
the range of 0.958-0.994, which shows that the disso-
lution data fitted well to Higuchi’s square root of time
equation confirming the release followed diffusion
mechanism. Kinetic data also treated for Peppas equa-
tion, the slope (n) values ranges from 0.871-1.479 that
shows Non-Fickian diffusion mechanism with super
case-II transport system.
Polynomial equations were derived for Wetting
time,
Disintegrating time, t50%
and t90%
values by back-
ward stepwise linear regression analysis using PCP
Disso software and Response surface plots were con-
structed using SIGMAPLOT V13 software. The Re-
sponse surface plots were shown in Fig.7-10 for Wet-
ting time, Disintegrating time, t50%
and t90%
using X1
and X2
on both the axes respectively. The dissolution
data (Kinetic parameters) of factorial formulations F1
to F9
are shown in Table 5. Polynomial equation for 3²
full factorial designs is given in Equation
Y= b0
+b1
X1
+b2
X2
+b12
X1
X2
+b11
X1
²+b22
X2
²…
Where, Y is dependent variable, b0
arithme-
tic mean response of nine batches, and b1
estimated
co-efficient for factor X1
. The main effects (X1
and X2
)
represent the average result of changing one factor
at a time from its low to high value. The interaction
term (X1
X2
) shows how the response changes when
two factors are simultaneously changed. The polyno-
mial terms (X1
² and X2
²) are included to investigate
non-linearity. Validity of derived equations was veri-
fied by preparing two check point formulations of in-
termediate concentration(C1
, C2
).
The equations for Wetting time, Disintegrating
time, t50%
and t90%
developed as follows,
Y1
= 49.00-13.25X1
-19X2
+8.75 X1
2
+17.5 X2
2
(for
Wetting time)
Y2
= 62.33-16.25X1
-19X2
+11.75 X1
2
+13.5 X2
2
(for
Disintegration time)
Y3
= 3.441-0.605X1
-0.331X2
+0.017 X1
X2
+0.407
X1
2
+0.07 X2
2
(for t50%
)
Y4
= 11.435-2.01X1
-1.099X2
+0.057 X1
X2
+1.35
X1
2
+0.233 X2
2
(for t90%
)
The positive sign for co-efficient of X1
in Y1,
Y2,
Y3
and Y4
equations indicates that, as the concentration
of crospovidone decreases, Wetting time,
Disintegrat-

6. 20
Kumar Gunda, Suresh Kumar
ing time, t50%
and t90%
value increases. In other words
the data demonstrate that both X1
(quantity of crospo-
vidone) and X2
(quantity of croscarmellose sodium)
affect the time required for drug release (Wetting time,
Disintegrating time, t50%
and t90%
). From the results it
can be concluded that, and increase in the quantity of
the superdisintegrant leads to decrease in disintegra-
tion time of the dosage form and drug release pattern
may be changed by appropriate selection of the X1
and X2
levels. The dissolution parameters for predict-
ed from the polynomial equations derived and those
actual observed from experimental results are sum-
marized in Table 6. The closeness of predicted and
observed values for Wetting time,
Disintegrating time,
t50%
and t90%
indicates validity of derived equations for
dependent variables. The response surface plots were
presented to show the effects X1
and X2
on Wetting
time,
Disintegrating time,
t50%
and t90%.
The final best
(Optimized) formulation (F1
) is compared with mar-
keted product (SOLIAN-100) shows similarity factor
(f2
) 85.384, difference factor (f1
) 2.098 (There is no
significant difference in drug release because p<0.05).
Comparative dissolution plots for best formulation
(F1
) and marketed product shown in fig 11.
CONCLUSION
The present research work envisages the applica-
bility of superdisintegrants such as crospovidone and
croscarmellose sodium in the design and develop-
ment of fast dissolving tablet formulations of Amisul-
pride utilizing the 32
factorial design. From the results
it was clearly understand that as the concentration of
superdisintegrant increases the release rate of drug
was RAPID (Improved Solubility) and both of these
superdisintegrants can be used in combination since
do not interact with the drug which may be more
helpful in achieving the desired fast dissolving of the
dosage form for rapid action and improved bioavail-
ability. The optimized formulation followed Higuchi’s
kinetics while the drug release mechanism was found
to be Non-Fickian diffusion with super case-II trans-
port, first order release type. On the basis of evalu-
ation parameters, the optimized formulation F1
may
be used for the effective management of psychoses,
paranoid, productive schizophrenias, dysthymia. This
may improve the patient compliance by showing rapid
action via disintegration without difficult in swallow-
ing and side effects which will ultimately improve the
therapeutic outcome. We could be able to minimize
the per oral cost of the Formulation.
Table 3: Post-compression parameters for the formulations (± indicates standard deviation)
S.No Formulation
Code
Hardness
(kg/cm2
)
n=3
Thickness
(mm)
n=3
Friability (%)
n=3
Drug
Content (%)
n=3
Wetting
Time( sec)
n=3
Disintegration
Time (sec) n=3
1 F1
3.49±0.38 3.11±0.16 0.575±0.12 99.24±0.25 25.5±1.3 35.5±1.5
2 F2
3.41±0.57 3.08±0.76 0.585±0.13 98.68±0.30 27±1.4 41.0±1.6
3 F3
3.65±0.42 3.06±0.44 0.465±0.1 97.85±0.50 63.5±1.6 73.5±1.8
4 F4
3.60±0.24 3.08±0.67 0.585±0.12 99.04±.40 30±1.4 40.0±1.4
5 F5
3.55±0.43 3.05±1.27 0.595±0.13 98.48±0.90 31.5±1.5 45.5±1.5
6 F6
3.81±0.28 3.03±0.95 0.475±0.05 97.65±0.70 68±1.7 78.01±1.7
7 F7
3.35±0.38 3.07±0.54 0.375±0.13 98.72±0.25 52±1.3 68.0±1.4
8 F8
3.31±0.57 3.04±1.14 0.385±0.13 98.16±0.30 53.5±1.5 73.5±1.5
9 F9
3.55±0.43 3.02±0.82 0.265±0.14 97.33±0.50 90±1.6 106.0±1.7

7. 21
FABAD J. Pharm. Sci., 43, 2, 15-25, 2018
Table 4: Regression analysis data of 32
factorial design formulations of Amisulpride fast dissolving tablets
S.NO
Formulation
Code
KINETIC PARAMETERS
ZERO ORDER FIRST ORDER HIGUCHI
KORSMEYER-
PEPPAS
a b r a b r a b r a b r
1 F1
18.395 7.750 0.941 2.016 0.112 0.988 0.137 29.718 0.992 1.445 0.532 0.984
2 F2
19.434 7.340 0.932 2.000 0.103 0.999 1.209 28.452 0.994 1.459 0.504 0.986
3 F3
10.734 7.846 0.968 2.035 0.091 0.987 5.690 29.019 0.985 1.233 0.719 0.985
4 F4
20.315 7.295 0.922 1.993 0.105 0.994 1.788 28.469 0.990 1.466 0.500 0.977
5 F5
21.355 6.885 0.906 1.977 0.096 0.993 3.134 27.202 0.985 1.479 0.474 0.961
6 F6
12.656 7.391 0.956 2.018 0.086 0.996 3.765 27.769 0.988 1.255 0.688 0.979
7 F7
9.462 7.695 0.974 2.020 0.078 0.983 6.166 28.241 0.984 1.212 0.724 0.986
8 F8
10.504 7.284 0.973 2.010 0.073 0.998 4.818 26.973 0.991 1.228 0.694 0.993
9 F9 1.799 7.792 0.986 2.043 0.066 0.974 11.722 27.542 0.958 0.871 1.043 0.986
Table 5: Dissolution parameters of Amisulpride fast dissolving tablets 3² full factorial design batches
S.NO
FORMULATION
CODE
KINETIC PARAMETERS
t1/2
(Min) t90%
(Min) WT(Sec) DT(Sec)
1 F1
2.679 8.902 25.5 35.5
2 F2
2.922 9.711 27 41
3 F3
3.315 11.015 63.5 73.5
4 F4
2.872 9.545 30 40
5 F5
3.123 10.377 31.5 45.5
6 F6
3.515 11.681 68 78
7 F7
3.850 12.794 52 68
8 F8
4.138 13.750 53.5 73.5
9 F9
4.555 15.136 90 106
Table 6: Dissolution parameters for predicted and observed values for check point formulations
FORMULATION
CODE
PREDICTED VALUE ACTUAL OBSERVED VALUE
WT(Sec) DT(Sec)
t50%
(min)
t90%
(min)
WT(Sec) DT(Sec)
t50%
(min)
t90%
(min)
C1
71.688 86.268 4.033 13.395 72.03 85.75 4.128 13.524
C2
39.438 51.018 3.097 10.295 40.02 52.34 3.121 10.351

8. 22
Kumar Gunda, Suresh Kumar
Figure 1. Comparative Zero order plots for Formulation F1
-F9
Figure 2. Comparative First order plots for Formulation F1
-F9
Figure 3. Comparative Higuchi plots for Formulation F1
-F9

9. 23
FABAD J. Pharm. Sci., 43, 2, 15-25, 2018
Figure 4. Comparative Korsemeyer-Peppas plots for Formulation F1
-F9
Figure 5. Wetting Time Chart for Formulation F1
-F9
Figure 6. Disintegration Time Chart for Formulation F1
-F9

10. 24
Kumar Gunda, Suresh Kumar
Figure 7. Response Surface plot for Wetting Time Figure 8. Response Surface plot for Disintegration Time
Figure 9. Response Surface plot for t50%
Figure 10. Response Surface plot for t90%
Figure 11. Comparative Dissolution plots for F1
, Solian-100

11. 25
FABAD J. Pharm. Sci., 43, 2, 15-25, 2018
ACKNOWLEDGEMENTS:
The author would like to thank the Principal,
Management & Staff of Narasaraopeta Institute of
Pharmaceutical Sciences, Narasaraopet, Guntur (D.t),
A.P., India for providing support for successful com-
pletion of research work.
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ABBREVATIONS AND SYMBOLS USED
ODT - Oral Disintegrating Tablet
CCS - CrosCarmellose Sodium
CP - Crospovidone
Kg - Kilo Gram
Cm - Centi Meter
% - Percentage
mg - milli gram
ml - milli litre
%CDR - Percentage Cumulative Drug Release
BCS - Biopharmaceutical Classification
UR - Un Released
Min - Minute
ºC - Degree Centigrade
mm - milli meter
t1/2
- Half Life
DT - Disintegration Time
WT - Wetting Time
t50%
- Time taken to release 50% drug from dos-
age form
t90%
- Time taken to release 90% drug from dos-
age form
Running title: Formulation and Evaluation of
Fast Dissolving Tablets of Amisulpride.